Inhibition of acid-induced hyperaemia in the rat stomach by endogenous NK2 receptor ligands.
Since exogenously applied tachykinins (substance P and neurokinin A) prevent the neurogenic hyperaemia which is elicited by acid back-diffusion in the rat stomach, we investigated whether endogenous tachykinins would act in a similar manner. Acid back-diffusion, induced by perfusing the stomach with 15% ethanol in the presence of 0.05 M HCI, increased gastric mucosal blood flow (GMBF) by 60-100% as determined by hydrogen clearance in urethane-anaesthetized rats. This response remained unchanged after pretreatment with the tachykinin NK1 receptor antagonist SR 140,333 (300 nmol/kg) but tended to be enhanced by the NK2 receptor antagonist MEN 10,627 (200 nmol/kg). When given during ongoing acid back-diffusion, MEN 10,627 significantly enhanced the acid-evoked vasodilatation as compared with vehicle or SR 140,333. We conclude that endogenously released tachykinins, acting via NK2 receptors, limit the gastric hyperaemic response to acid.
Heinemann
A
A
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Sattler
V
V
Jocic
M
M
Holzer
P
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005744:Gastric Acid / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006940:Hyperemia / Q000139:chemically induced / Q000517:prevention & control*; D008024:Ligands; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013270:Stomach / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D008024:Ligands; D010456:Peptides, Cyclic; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C085215:SR 140333; C090951:MEN 10627